Bruce Bean, Ph.D.
Professor of Neurobiology
Neurobiology, Goldenson Bldg., Rm. 301
220 Longwood Ave.
Boston, MA 02115
Neurons generate electrical signals by the activity of ion channels, molecular pores in the membrane of the neuron. We are interested in how the electrical activity of particular types of mammalian neurons depends on the particular combination of ion channels present in the neurons, both in normal operation of the brain and in pathophysiological conditions such as epilepsy and neuropathic pain.
We are especially interested in the ionic mechanisms that underlie pacemaking, the spontaneous firing of central neurons in the absence of synaptic input. Electrical signaling in the central nervous system is characterized by oscillatory activity at all levels, and this originates as spontaneous firing at the single cell level. To study pacemaking in central neurons, we prepare isolated neurons from particular brain regions and use the voltage-clamp technique together with various drugs and toxins to identify currents carried by different ion channels.
We are also interested in the properties of specific types of ion channels that endow neurons with specialized firing properties, such as the ability of “fast-spiking” cortical interneurons to fire unusually rapidly, and in the ability of modulatory neurotransmitters like serotonin, dopamine, and acetylcholine to modify neuronal excitability by modulating activity of voltage-dependent ion channels.
Central neurons currently being studied include cerebellar Purkinje neurons, hippocampal and cortical pyramidal neurons, cortical interneurons, midbrain dopaminergic neurons, and hypothalamic neurons that control feeding, sleep, and circadian rhythms. Ion channels of particular interest include voltage-dependent sodium channels, voltage-dependent calcium channels, Kv3-family potassium channels, Kv2-family potassium channels, and BK calcium-activated potassium channels. Transmitters of particular interest include acetycholine, dopamine, orexin, ghrelin, and leptin.
Work in the laboratory is based mainly on electrophysiological recording from central neurons, both in brain slice and after acute dissociation. The electrophysiological work is complemented by immunohistochemical studies examining the subcellular expression patterns of various ion channels. The work relies on pharmacological tools, and we are also interested in the pharmacology of ion channels for clinical therapy. We are exploring how antiepileptic drugs can prevent abnormal firing patterns in cortical circuits without disrupting normal firing, with the goal of improving antiepileptic activity while minimizing side effects. Also, we are collaborating with Clifford Woolf’s laboratory to develop treatments for pain and itch based on novel sodium and calcium channel blockers
For a complete listing of publications click here.